Studies are being directed toward understanding the major histocompatibility complex, the structure and function of the products of this complex, and manipulations of immune responses to these products. Current studies include: 1) Characterization of major histocompatibility antigens: Congenic resistant strains of mice are developed, maintained, and used in serologic and immunochemical analyses of the MHC products of the mouse. 2) Studies of monoclonal antibodies to H-2 and Ia antigens: Hybridoma cell lines are produced by fusion of immune mouse spleen cells with mouse myeloma cells. The monoclonal anti-H-2 and anti-Ia antibodies produced by these hybridomas are analyzed by serologic and immunochemical means and are used to further characterize the fine structure of the MHC. 3) Characterization of receptor sites for histocompatibility antigens: Anti-idiotypic antisera are being produced against anti-H-2 and anti-Ia hybridoma antibodies, and the effects of these antisera on in vitro and in vivo parameters of histocompatibility are being assessed. 4) Mechanism of tolerance to H-2 and Ia antigens: The humoral and cellular responses of radiation bone marrow chimeras are being examined, and the mechanism for maintenance of tolerance in these animals is being studied.